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The apical junctional complex and tight junctions in the small intestine. ZO-1 = Zonula occludens-1; ZO-2 = Zonula occludens-2.
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The novel corona virus that is now known as (SARS-CoV-2) has killed more than six million people worldwide. The disease presentation varies from mild respiratory symptoms to acute respiratory distress syndrome and ultimately death. Several risk factors have been shown to worsen the severity of COVID-19 outcomes (such as age, hypertension, diabetes...
Context in source publication
Context 1
... intestinal epithelial cells are connected inter-cellularly by tight semi-permeable gates that allow the influx of ions and prevent the passage of pathogens. As shown in Figure 1, these adjacent structures are called "apical junctional complexes" (AJC). AJCs are composed of tight junctions, and adherens junctions [69]. ...
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Citations
... This condition has been strongly associated with various cardiovascular, cerebrovascular, and metabolic disorders. In recent years, extensive clinical observational studies have indicated that individuals with OSA may be more susceptible to COVID-19 infection and experience poorer outcomes [7][8][9][10][11][12][13][14][15]. Furthermore, two meta-analyses have revealed that OSA is associated with a 2.0 and 1.7 times increased risk of severe COVID-19, respectively [16,17]. ...
... Furthermore, given the concurrent involvement and impact on the respiratory system in both conditions, certain studies postulate that individuals with pre-existing OSA are at an elevated risk of morbidity and mortality upon exposure to SARS-CoV-2 due to an excessive inflammatory response [19,20]. Moreover, a review conducted by Mashaqi et al. suggested that alterations in the gut microbiota, which occur in the context of COVID-19 and OSA, can exacerbate systemic inflammation by facilitating the translocation of microorganisms across a compromised intestinal barrier [8]. Overall, the current theories and hypotheses fail to provide a comprehensive elucidation of the intrinsic molecular mechanisms underlying the association between OSA and COVID-19. ...
... Inflammation constitutes a hallmark feature of both OSA and SARS-CoV-2 infections. Hypotheses suggest that alterations in the gut microbiota, which are associated with COVID-19 and OSA, may compromise the integrity of the intestinal barrier, thereby facilitating the translocation of bacteria into the systemic circulation and subsequently promoting systemic inflammation [8]. Notably, systemic inflammation is particularly pronounced in the context of COVID-19. ...
Background
The prevalence of obstructive sleep apnea (OSA) was found to be higher in individuals following COVID-19 infection. However, the intricate mechanisms that underscore this concomitance remain partially elucidated. The aim of this study was to delve deeper into the molecular mechanisms that underpin this comorbidity.
Methods
We acquired gene expression profiles for COVID-19 (GSE157103) and OSA (GSE75097) from the Gene Expression Omnibus (GEO) database. Upon identifying shared feature genes between OSA and COVID-19 utilizing LASSO, Random forest and Support vector machines algorithms, we advanced to functional annotation, analysis of protein–protein interaction networks, module construction, and identification of pivotal genes. Furthermore, we established regulatory networks encompassing transcription factor (TF)-gene and TF-miRNA interactions, and searched for promising drug targets. Subsequently, the expression levels of pivotal genes were validated through proteomics data from COVID-19 cases.
Results
Fourteen feature genes shared between OSA and COVID-19 were selected for further investigation. Through functional annotation, it was indicated that metabolic pathways play a role in the pathogenesis of both disorders. Subsequently, employing the cytoHubba plugin, ten hub genes were recognized, namely TP53, CCND1, MDM2, RB1, HIF1A, EP300, STAT3, CDK2, HSP90AA1, and PPARG. The finding of proteomics unveiled a substantial augmentation in the expression level of HSP90AA1 in COVID-19 patient samples, especially in severe conditions.
Conclusions
Our investigation illuminate a mutual pathogenic mechanism that underlies both OSA and COVID-19, which may provide novel perspectives for future investigations into the underlying mechanisms.
... 295,296 This balanced relationship may be disrupted by changes in the composition of the microbiota, known as dysbiosis. Current studies have found that gut dysbiosis might play a role in OSAS-associated morbidities, such as systemic hypertension, 297-300 metabolic disorders, 301-303 neurological diseases, 304 COVID-19, 305 and atherosclerotic heart disease. 306 The gut is the largest immune organ and the largest microecosystem in the human body. ...
Obstructive sleep apnea syndrome (OSAS) is a common breathing disorder in sleep in which the airways narrow or collapse during sleep, causing obstructive sleep apnea. The prevalence of OSAS continues to rise worldwide, particularly in middle-aged and elderly individuals. The mechanism of upper airway collapse is incompletely understood but is associated with several factors, including obesity, craniofacial changes, altered muscle function in the upper airway, pharyngeal neuropathy, and fluid shifts to the neck. The main characteristics of OSAS are recurrent pauses in respiration, which lead to intermittent hypoxia (IH) and hypercapnia, accompanied by blood oxygen desaturation and arousal during sleep, which sharply increases the risk of several diseases. This paper first briefly describes the epidemiology, incidence, and pathophysiological mechanisms of OSAS. Next, the alterations in relevant signaling pathways induced by IH are systematically reviewed and discussed. For example, IH can induce gut microbiota (GM) dysbiosis, impair the intestinal barrier, and alter intestinal metabolites. These mechanisms ultimately lead to secondary oxidative stress, systemic inflammation, and sympathetic activation. We then summarize the effects of IH on disease pathogenesis, including cardiocerebrovascular disorders, neurological disorders, metabolic diseases, cancer, reproductive disorders, and COVID-19. Finally, different therapeutic strategies for OSAS caused by different causes are proposed. Multidisciplinary approaches and shared decision-making are necessary for the successful treatment of OSAS in the future, but more randomized controlled trials are needed for further evaluation to define what treatments are best for specific OSAS patients.
... Moreover, since the incidence of sleep apnea has been increasing during the coronavirus disease 2019 era, it is important to recognize and treat it. [1][2][3][4] Recently, there has been growing interest in sleep apnea as a systemic inflammatory disease. 5,6 Inflammation is an important mechanism by which sleep apnea leads to serious complications, including hypertension, arrhythmia, and stroke. ...
... It revealed that plasma FFAs and triglycerides increased after 60 min intervention [211]. Moreover, induced chronic intermittent hypoxic (CIH) (sleep apnea, a hallmark of obstructive sleep apnea, OSA) [212,213] has aggravated insulin resistance in obese mice and promoted steatohepatitis, thereby exacerbating obesity [214][215][216][217][218]. As most of these studies have used hypoxic to mimic the status of pathological hypoxic, chronic intermittent hypoxic caused by OSA in obese patients may be one of the underlying mechanisms of the obesity-morbidities paradox [219]. These findings suggest the concentration and duration of hypoxic in patients with sleep apnea syndrome should be critically assessed for the appropriate interventions. ...
The global epidemic of obesity is tightly associated with numerous comorbidities, such as type II diabetes, cardiovascular diseases and the metabolic syndrome. Among the key features of obesity, some studies have suggested the abnormal expansion of adipose-tissue-induced local endogenous hypoxic, while other studies indicated endogenous hyperoxia as the opposite trend. Endogenous hypoxic aggravates dysfunction in adipose tissue and stimulates secretion of inflammatory molecules, which contribute to obesity. In contrast, hypoxic exposure combined with training effectively generate exogenous hypoxic to reduce body weight and downregulate metabolic risks. The (patho)physiological effects in adipose tissue are distinct from those of endogenous hypoxic. We critically assess the latest advances on the molecular mediators of endogenous hypoxic that regulate the dysfunction in adipose tissue. Subsequently we propose potential therapeutic targets in adipose tissues and the small molecules that may reverse the detrimental effect of local endogenous hypoxic. More importantly, we discuss alterations of metabolic pathways in adipose tissue and the metabolic benefits brought by hypoxic exercise. In terms of therapeutic intervention, numerous approaches have been developed to treat obesity, nevertheless durability and safety remain the major concern. Thus, a combination of the therapies that suppress endogenous hypoxic with exercise plans that augment exogenous hypoxic may accelerate the development of more effective and durable medications to treat obesity and comorbidities.
... Previous studies (Yonker et al, 2021;Giron et al., 2021;Oliva et al., 2021) have linked higher intestinal translocation with severe cases of COVID-19, describing a higher abundance of bacterial components in the bloodstream compared to milder cases. It has been suggested that microbial translocation, intestinal dysbiosis and underlying inflammatory processes might have a synergistic effect on systemic inflammation and high cytokine levels described in severe COVID-19 infections (Cardinale et al., 2020;Vignesh et al., 2020;Uzzan et al., 2020;Mashaqi et al., 2022). ...
Zonulin has previously been related to intestinal permeability in various inflammatory diseases, and more recently to the physiopathology of severe COVID-19 infections. We analysed serum samples from a previous study of a Peruvian cohort of hospitalised COVID-19 patients, for the quantification of zonulin by sandwich ELISA. Comparisons with clinical data, haematological and biochemical parameters and cytokine/chemokine levels were made. We found higher baseline zonulin levels in deceased patients, and zonulin was associated with fatal outcome in multivariable analyses, even after adjustment for age, gender, and obesity. There were also positive correlations between zonulin, creatinine, D-dimer values and prothrombin time, while inverse correlations were found for Sa/FiO2 ratio and CCL5 (RANTES). Further longitudinal studies are recommended to analyse the variation of zonulin levels over time as well as their relationship with long-COVID.
... In the case of subjects genetically predisposed to autoimmune diseases, changes in the structure and function of their intestinal microbiota caused by environmental factors will disrupt the function of the zonulin-dependent intestinal barrier (inadequate control of antigen flows), i.e., zonulin-dependent loss of the intestinal mucosal barrier, leading to "leaky gut" or the "permeable intestine" and a dysfunctional immune response of the mucosa, with implications for autoimmunity and chronic inflammatory diseases [134,139,[142][143][144]. ...
Celiac disease (CD) comprises over 1% of the world's population and is a chronic multisystem immune-mediated condition manifested by digestive and/or extradigestive symptoms caused by food intake of gluten. This review looked at the risk of children diagnosed with CD developing SARS-CoV-2 infection and possible severe forms of COVID-19. A better understanding of the interaction and effects of SARS-CoV-2 infection in CD is very important, as is the role of environmental and genetic factors, but especially the molecular mechanisms involved in modulating intestinal permeability with impact on autoimmunity. CD inspired the testing of a zonulin antagonist for the fulminant form of multisystem inflammatory syndrome in children (MIS-C) and paved the way for the discovery of new molecules to regulate the small intestine barrier function and immune responses. Original published works on COVID-19 and CD, new data and points of view have been analyzed because this dangerous virus SARS-CoV-2 is still here and yet influencing our lives. Medical science continues to focus on all uncertainties triggered by SARS-CoV-2 infection and its consequences, including in CD. Although the COVID-19 pandemic seems to be gradually extinguishing, there is a wealth of information and knowledge gained over the last two years and important life lessons to analyze, as well as relevant conclusions to be drawn to deal with future pandemics. Zonulin is being studied extensively in immunoengineering as an adjuvant to improving the absorption of new drugs and oral vaccines.
The composition, viability and metabolic functionality of intestinal microbiota play an important role in human health and disease. Studies on intestinal microbiota are often based on fecal samples, because these can be sampled in a non-invasive way, although procedures for sampling, processing and storage vary. This review presents factors to consider when developing an automated protocol for sampling, processing and storing fecal samples: donor inclusion criteria, urine–feces separation in smart toilets, homogenization, aliquoting, usage or type of buffer to dissolve and store fecal material, temperature and time for processing and storage and quality control. The lack of standardization and low-throughput of state-of-the-art fecal collection procedures promote a more automated protocol. Based on this review, an automated protocol is proposed. Fecal samples should be collected and immediately processed under anaerobic conditions at either room temperature (RT) for a maximum of 4 h or at 4 °C for no more than 24 h. Upon homogenization, preferably in the absence of added solvent to allow addition of a buffer of choice at a later stage, aliquots obtained should be stored at either −20 °C for up to a few months or −80 °C for a longer period—up to 2 years. Protocols for quality control should characterize microbial composition and viability as well as metabolic functionality.
Background:
Obstructive sleep apnea (OSA) syndrome is associated with a high mortality, and blood oxygen indexes play an important role in evaluating this disease. The objective of this study was to explore the value of blood oxygen indexes, including minimum oxygen saturation (LSpO2), oxygen reduction index (ODI) and time spent with oxygen saturation below 90% (TS 90%), as diagnostic markers for OSA syndrome.
Methods:
In this retrospective study, 320 patients with OSA treated in Ningbo First Hospital from June 2018 to June 2021 were included and divided into mild, moderate, and severe groups according to the severity of the condition (n = 104, 92, and 124, respectively). The blood oxygen indexes as well as the apnea-hypopnea index (AHI) were compared. The Spearman correlation analysis was performed to explore the relationship between the parameters. Receiver operating characteristic curves were generated to evaluate the diagnostic value of the blood oxygen indexes for OSA syndrome.
Results:
There were significant differences in body weight, body mass index, and blood pressure before and after sleep among the groups (P < 0.05). LSpO2 levels followed a pattern with the severe group showing the lowest values, followed by the moderate group, and then the mild group, whereas ODI and TS 90% levels showed the opposite (P < 0.05). Spearman correlation analysis showed that AHI, ODI, TS 90% were positively correlated with severity of OSA, whereas LSpO2 was negatively correlated with severity of OSA. ODI showed a high diagnostic value for OSA (area under curve (AUC) = 0.823, 95% CI: 0.730-0.917). TS 90% showed a high diagnostic value for OSA (AUC = 0.872, 95% CI: 0.794-0.950). LSpO2 showed high accuracy in diagnostic value for OSA (AUC = 0.716, 95% CI: 0.596-0.835). The combination of the 3 indexes demonstrated a high diagnostic value for OSA (AUC = 0.939, 95% CI: 0.890-0.989). The diagnostic value of the combined signature was found to be significantly higher compared to the value of individual indexes (P < 0.05).
Conclusion:
The evaluation of the severity of OSA should not rely solely on a single observation index, but rather on a combination of ODI, LSpO2 and TS 90%. This combined diagnostic signature can provide a more comprehensive assessment of the patient's condition and serve as an alternative diagnostic basis to ensure timely diagnosis and appropriate clinical treatment for OSA.
